Biodegradable drug delivery systems (e.g., including microcapsules, microspheres, nanocapsules, nanoparticles, and biodegradable implants) are used to release drugs for an extended period of time. The biodegradable delivery systems are often prepared using biodegradable polyesters such as poly (ε-caprolactone), poly(ε-caprolactone-co-DL-lactic acid), poly(ε-caprolactone-co-glycolic acid), poly(DL-lactic acid), and poly(DL-lactide-co-glycolide).
Degradation of the polyesters [e.g., poly(DL-lactic acid), and poly(DL-lactide-co-glycolide)] has been reported to proceed by nonenzymatic random hydrolytic cleavage of ester linkages by an autocatalytic process. The biodegradable polyesters degrade slowly into acidic lower molecular weight fragments, and ultimately into lactic and glycolic acid monomers which are excreted through normal metabolic pathways. Upon incorporation of the polyesters into microspheres, acidic degradants created by polymer degradation result in an extremely acidic microenvironment in the microsphere. The acidic microenvironment induced by the polymer degradants often destabilizes and causes deterioration of the biological activity of the incorporated active substances in the microspheres.
Thus, there remains a need for a compositions and methods for improving the stability of active agents incorporated into microspheres. The invention provides such compositions and methods. These and other advantages of the present invention, as well as additional inventive features, will be apparent from the description of the invention provided herein.